Iodine-containing pharmaceuticals

Influence of Iodine-Containing Pharmaceuticals on Iodine Status and Thyroid Function Iodine-Induced Hyperthyroidism and Hypothyroidism... 

Iodine is an essential component of thyroid hormones, and iodine deficiency can lead to severe hypothyroidism. On the other hand, excessive iodine intake also results in thyroid dysfunction in certain persons. Coindent described the first case of iodine-induced hyperthyroidism in 1821 (Fradkin and Wolff, 1983), and Hurxthal (1945) reported the first case of iodine-induced hypothyroidism. Ingestion of iodine-rich foods, such as seaweed, can cause hyperthyroidism, and the incidence of hyperthyroidism showed an increase in regions of dietary iodine deficiency after prophylactic iodization of bread or salt. Iodine-containing pharmaceuticals, such as povidone-iodine (PVP-I), radiographic contrast media and amiodarone, are a major source of excessive iodine intake (Wolff, 1969 Fradkin and Wolff, 1983 Markou et aL, 2001 Roti and degli Uberti, 2001). 

The effect of excessive iodine intake on thyroid function, the role of iodine-containing pharmaceuticals, and clinical aspects of iodine-induced thyroid dysfunction are discussed in this review. 

Iodine-Containing Pharmaceuticals that Induce Thyroid Dysfunction... 

There are many iodine-containing pharmaceuticals that can cause thyroid dysfunction. The majority of patients with such drug-induced thyroid dysfunction are found among those treated with inorganic iodine preparations, such as potassium iodide, sodium iodide, hydrogen iodide, or Lugols solution (Wolff, 1969 Fradkin and Wolff 1983). These days, however, the major sources of iodine... 

Iodine-induced hypothyroidism usually improves within a few weeks after iodine withdrawal, but some patients require temporary hormone replacement therapy (Wemeau, 2002). Unless there is underlying Graves disease, patients with iodine-induced hyperthyroidism do not have exophthalmos (Fradkin and Wolff, 1983 Roti and degU Uberti, 2001). Unlike hypothyroidism, iodine-induced hyperthyroidism is often not self-limited, and medication is required in addition to discontinuation of iodine-containing pharmaceuticals (Rajatanavin et al, 1984). 

Development of iodine-induced thyroid dysfunction is influenced by a person s prior iodine intake. Cases of thyrotoxicosis being induced by contrast media are mainly reported in Europe or Australia, where dietary iodine levels are low, as described by Fradkin and Wolff (1983). Except for cases due to amiodarone, the incidence of iodine-induced hyperthyroidism is very low in regions where dietary iodine is adequate (Roti and degfl Uberti, 2001). Neonates treated with PVP-I often develop hypothyroidism in iodine-insufficient regions of Europe, but rarely do so in iodine-sufficient regions of the United States, as described by Brown et al. (1997). Thus, persons who five in areas where iodine is deficient in the diet are at risk of developing thyroid dysfunction induced by iodine-containing pharmaceuticals. 

There are many reasons why fetuses and newborn infants are more hkely to develop hypothyroidism due to iodine-containing pharmaceuticals. The abihty of the thyroid gland to escape from acute inhibition is defective in the fetus and neonate (Theodoropoulos et al, 1979), so both fetuses and newborns are sensitive to iodine overload. Also, the capacity to synthesize and release thyroid hormones is low in preterm babies (Ares et al, 1997). 

Amiodarone also has intrinsic effects on the thyroid and thyroid hormone production besides those related to excessive iodine intake (Table 96.4), and this means that it induces thyroid dysfunction more frequently than any other iodine-containing pharmaceutical. 

Use of iodine-containing pharmaceuticals should be avoided, if possible, in newborn infants and pregnant women, especially in areas with a low dietary iodine intake. Individuals at risk for iodine-induced thyroid dysfunction, such as patients with previous thyroid disease or neonates, should be observed carefully to detect manifestations of thyroid dysfunction when they are treated with iodine-containing pharmaceuticals. 

Iodine-containing pharmaceuticals, such as PVP-I, radiographic contrast media and amiodarone, are a major cause of excessive iodine intake inducing thyroid dysfunction. 

Iodine Iodine is a volatile purple-black solid with a beautiful metallic sheen. As the least reactive halogen, iodine is safe to handle and is widely used as a skin disinfectant. It was first prepared in 1811 from seaweed ash, but commercially useful deposits of the iodine-containing minerals lautarite (CaIC>3) and dietzeite [7 Ca( 103)2 8 CaCr04] were subsequently found in Chile. Iodine is used in the preparation of numerous organic compounds, including dyes and pharmaceutical agents, but there is no one single use of major importance. 

Pharmaceutical compounds containing complexes of molecular iodine have a wide spectrum of antibacterial and antiviral activity, including HIV. However, all known iodine-containing drags are characterized as highly toxic substances and therefore in fact are not used in medical practice for parenteral application. 

Organic halides are important synthetic intermediates in numerous reactions. They are also important due to the variety of radiohalogen-containing pharmaceuticals that have been developed in recent years [1-3]. The trialkylboranes prepared via hydroboration are conveniently converted to alkyl halides when 1 equiv of sodium hydroxide or sodium methoxide in methanol is added to a mixture of 1 mol of organoborane and 1 mol of iodine. The reaction becomes instantaneous and affords the corresponding alkyl halides. A second mole of iodine and base react similarly (Eq. 13.1) [4-6], ljut the third alkyl resists the reaction under these conditions. 

Medical Usage. Isopropyl alcohol is also used as an antiseptic and disinfectant for home, hospital, and industry (see Disinfectants and antiseptics). It is about twice as effective as ethyl alcohol in these appHcations (153,154). Rubbing alcohol, a popular 70 vol % isopropyl alcohol-in-water mixture, exemplifies the medicinal use of isopropyl alcohol. Other examples include 30 vol % isopropyl alcohol solutions for medicinal liniments, tinctures of green soap, scalp tonics, and tincture of mercurophen. It is contained in pharmaceuticals, eg, local anesthetics, tincture of iodine, and bathing solutions for surgical sutures and dressings. Over 200 uses of isopropyl alcohol have been tabulated (2). 

The seeds of Tamarindus indica contain polysaccharides which can be extracted with hot water and purified by precipitation with alcohol. The polysaccharide is composed of D-galactose, D-xylose, and D-glucose (Fig. 10). These xyioglucans have been named amyloids since they give a color reaction with iodine similar to starch. The xyioglucans from Tamarindus are gel-forming polysaccharides which are stable in a wide pH range. This type of polysaccharide is mainly used in food industry, but, in some cases, it has been pharmaceutically employed as a substitute for pectin. 

Pharmaceutical Incompat, (from Remington s Pharmaceutical Sciences) Aspirin forms a damp to pasty mass when triturated with acetanilide, phenacetin, antipyrine, amidopyrine, methenamine, phenol or phenyl salicylate. Powders containing aspirin with an alkali salt such as sodium bicarbonate become gummy on contact with atmospheric moisture. Hydrolysis oecnrs in admixture with salts contg water of crystallization. Solns of the alkaline acetates and citrates, as well as alkalies themselves, dissolve aspirin but the result -ing solns hydrolyze rapidly to form salts of acetic and salicylic acids. Sugar and glycerol have been shown to hinder this decompn. Aspirin very slowly liberates hydriodic acid from potassium or sodium iodide. Subsequent oxidation by air produces free iodine. 

A variety of radiotracers are used in clinical work, the most used isotopes being technetium-99m, iodine-131, tantalum-201, xenon-133, and indium-113m. The use of technetium, Tc, dominates, since it can be made to react with many substances having specific biological behavior. Tc is obtained from an isotope generator, which is based on the radioactive decay of radioactive molybdenum, Mo. Pharmaceuticals containing Tc are usually introduced by intravenous injection. Some radiopharmaceuticals may also be introduced orally, e.g., for those containing iodine this is the common procedure. 

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